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Cortical Proteins Associated With Cognitive Resilience in Community-Dwelling Older Persons
Open accessAbstract
Importance: Identifying genes and proteins for cognitive resilience (ie, targets that may be associated with slowing or preventing cognitive decline regardless of the presence, number, or combination of common neuropathologic conditions) provides a complementary approach to developing novel therapeutics for the treatment and prevention of Alzheimer disease and related dementias. Objective: To identify proteins associated with cognitive resilience via a proteome-wide association study of the human dorsolateral prefrontal cortex. Design, Setting, and Participants: This study used data from 391 community-dwelling older persons who participated in the Religious Orders Study and the Rush Memory and Aging Project. The Religious Orders Study began enrollment January 1, 1994, and the Rush Memory and Aging Project began enrollment September 1, 1997, and data were collected and analyzed through October 23, 2019. Exposures: Participants had undergone annual detailed clinical examinations, postmortem evaluations, and tandem mass tag proteomics analyses. Main Outcomes and Measures: The outcome of cognitive resilience was defined as a longitudinal change in cognition over time after controlling for common age-related neuropathologic indices, including Alzheimer disease, Lewy bodies, transactive response DNA-binding protein 43, hippocampal sclerosis, infarcts, and vessel diseases. More than 8000 high abundance proteins were quantified from frozen dorsolateral prefrontal cortex tissue using tandem mass tag and liquid chromatography-mass spectrometry. Results: There were 391 participants (273 women); their mean (SD) age was 79.7 (6.7) years at baseline and 89.2 (6.5) years at death. Eight cortical proteins were identified in association with cognitive resilience: a higher level of NRN1 (estimate, 0.140; SE, 0.024; P = 7.35 × 10-9), ACTN4 (estimate, 0.321; SE, 0.065; P = 9.94 × 10-7), EPHX4 (estimate, 0.198; SE, 0.042; P = 2.13 × 10-6), RPH3A (estimate, 0.148; SE, 0.031; P = 2.58 × 10-6), SGTB (estimate, 0.211; SE, 0.045; P = 3.28 × 10-6), CPLX1 (estimate, 0.136; SE, 0.029; P = 4.06 × 10-6), and SH3GL1 (estimate, 0.179; SE, 0.039; P = 4.21 × 10-6) and a lower level of UBA1 (estimate, -0.366; SE, 0.076; P = 1.43 × 10-6) were associated with greater resilience. Conclusions and Relevance: These protein signals may represent novel targets for the maintenance of cognition in old age.
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“consistent with prior studies indicating its association with a slower rate of cognitive decline independent of AD and related dementia pathologies.”
From Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes (2025) · cites this paper as [49]
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“Yu et al. paralleled these network results, identifying associations between cognitive resilience and cortical proteins involved in synaptic, metabolic, and neurogenic functions [142].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [142]
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Cites
Neurotrophins: Roles in Neuronal Development and Function
Huang, E. J., & Reichardt, L. F. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.677 · Cited by 4,394
Religious Orders Study and Rush Memory and Aging Project
Bennett, D. A., Buchman, A. S., Boyle, P. A., Barnes, L. L., Wilson, R. S., & Schneider, J. A. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179939 · Cited by 1,260
Self-citationThe neuropathology of probable Alzheimer disease and mild cognitive impairment
Schneider, J. A., Arvanitakis, Z., Leurgans, S. E., & Bennett, D. A. (2009) · Annals of Neurology · doi:10.1002/ana.21706 · Cited by 935
Self-citationPerson-specific contribution of neuropathologies to cognitive loss in old age
Boyle, P. A., Yu, L., Wilson, R. S., Leurgans, S. E., Schneider, J. A., & Bennett, D. A. (2018) · Annals of Neurology · doi:10.1002/ana.25123 · Cited by 508
Self-citationGearing, M., Mirra, S. S., Hedreen, J. C., Sumi, S. M., Hansen, L. A., & Heyman, A. (1995) · Neurology · doi:10.1212/wnl.45.3.461 · Cited by 381
Much of late life cognitive decline is not due to common neurodegenerative pathologies
Boyle, P. A., Wilson, R. S., Yu, L., Barr, A. M., Honer, W. G., Schneider, J. A., & Bennett, D. A. (2013) · Annals of Neurology · doi:10.1002/ana.23964 · Cited by 323
Self-citationNeural reserve, neuronal density in the locus ceruleus, and cognitive decline
Wilson, R. S., Nag, S., Boyle, P. A., Hizel, L. P., Yu, L., Buchman, A. S., Schneider, J. A., & Bennett, D. A. (2013) · Neurology · doi:10.1212/wnl.0b013e3182897103 · Cited by 283
Self-citationAntidepressant actions of the exercise-regulated gene VGF
Hunsberger, J. G., Newton, S. S., Bennett, A., Duman, C. H., Russell, D., Salton, S. R., & Duman, R. S. (2007) · Nature Medicine · doi:10.1038/nm1669 · Cited by 270
Neuritin: A gene induced by neural activity and neurotrophins that promotes neuritogenesis
Naeve, G. S., Ramakrishnan, M., Kramer, R., Hevroni, D., Citri, Y., & Theill, L. E. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.6.2648 · Cited by 255
Higher brain BDNF gene expression is associated with slower cognitive decline in older adults
Buchman, A. S., Yu, L., Boyle, P. A., Schneider, J. A., De Jager, P. L., & Bennett, D. A. (2016) · Neurology · doi:10.1212/wnl.0000000000002387 · Cited by 239
Self-citationRelation of neuropathology to cognition in persons without cognitive impairment
Bennett, D. A., Wilson, R. S., Boyle, P. A., Buchman, A. S., & Schneider, J. A. (2012) · Annals of Neurology · doi:10.1002/ana.23654 · Cited by 220
Self-citationWingo, A. P., Dammer, E. B., Breen, M. S., Logsdon, B. A., Duong, D. M., Troncosco, J. C., Thambisetty, M., Beach, T. G., Serrano, G. E., Reiman, E. M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09613-z · Cited by 211
Self-citationClinical-pathologic study of depressive symptoms and cognitive decline in old age
Wilson, R. S., Capuano, A. W., Boyle, P. A., Hoganson, G. M., Hizel, L. P., Shah, R. C., Nag, S., Schneider, J. A., Arnold, S. E., & Bennett, D. A. (2014) · Neurology · doi:10.1212/wnl.0000000000000715 · Cited by 165
Self-citationShared proteomic effects of cerebral atherosclerosis and Alzheimer’s disease on the human brain
Wingo, A. P., Fan, W., Duong, D. M., Gerasimov, E. S., Dammer, E. B., Liu, Y., Harerimana, N. V., White, B., Thambisetty, M., Troncoso, J. C., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0635-5 · Cited by 161
Self-citationUBA1: At the Crossroads of Ubiquitin Homeostasis and Neurodegeneration
Groen, E. J. N., & Gillingwater, T. H. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.08.003 · Cited by 157
White, L., Small, B. J., Petrovitch, H., Ross, G. W., Masaki, K., Abbott, R. D., Hardman, J., Davis, D., Nelson, J., & Markesbery, W. (2005) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988705281872 · Cited by 155
Synaptic proteins, neuropathology and cognitive status in the oldest-old
Head, E., Corrada, M. M., Kahle-Wrobleski, K., Kim, R. C., Sarsoza, F., Goodus, M., & Kawas, C. H. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.10.001 · Cited by 145
Nedivi, E., Fieldust, S., Theill, L. E., & Hevron, D. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.5.2048 · Cited by 124
Targeted brain proteomics uncover multiple pathways to Alzheimer's dementia
Yu, L., Petyuk, V. A., Gaiteri, C., Mostafavi, S., Young‐Pearse, T., Shah, R. C., Buchman, A. S., Schneider, J. A., Piehowski, P. D., Sontag, R. L., et al. (2018) · Annals of Neurology · doi:10.1002/ana.25266 · Cited by 124
Self-citationUbiquitination Acutely Regulates Presynaptic Neurotransmitter Release in Mammalian Neurons
Rinetti, G. V., & Schweizer, F. E. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3712-09.2010 · Cited by 101
Early life instruction in foreign language and music and incidence of mild cognitive impairment.
Wilson, R. S., Boyle, P. A., Yang, J., James, B. D., & Bennett, D. A. (2014) · Neuropsychology · doi:10.1037/neu0000129 · Cited by 101
Self-citationCognitive reserve, presynaptic proteins, and dementia in the elderly
Honer, W. G., Barr, A. M., Sawada, K., Thornton, A. E., Morris, M. C., Leurgans, S. E., Schneider, J. A., & Bennett, D. A. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.38 · Cited by 100
Self-citationNormative Cognitive Decline in Old Age
Wilson, R. S., Wang, T., Yu, L., Bennett, D. A., & Boyle, P. A. (2020) · Annals of Neurology · doi:10.1002/ana.25711 · Cited by 97
Self-citationAbnormal α-synuclein interactions with rab3a and rabphilin in diffuse Lewy body disease
Dalfó, E., Barrachina, M., Rosa, J. L., Ambrosio, S., & Ferrer, I. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.01.001 · Cited by 94
Loss of SNAP‐25 and rabphilin 3a in sensory‐motor cortex in Huntington’s disease
Smith, R. A., Klein, P., Koc‐Schmitz, Y., Waldvogel, H. J., Faull, R. L. M., Brundin, P., Plomann, M., & Li, J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04703.x · Cited by 87
Decker, M., Adamska, M., Cronin, A., Giallonardo, F. D., Burgener, J., Marowsky, A., Falck, J. R., Morisseau, C. H. P., Hammock, B. D., Gruzdev, A., et al. (2012) · Journal of Lipid Research · doi:10.1194/jlr.m024448 · Cited by 86
Age, Alzheimer's disease and dementia in the Baltimore Longitudinal Study of Ageing
Dolan, D., Troncoso, J., Resnick, S. M., Crain, B. J., Zonderman, A. B., & O'Brien, R. J. (2010) · Brain · doi:10.1093/brain/awq141 · Cited by 70
Bennett, D. A. (2017) · PLoS Medicine · doi:10.1371/journal.pmed.1002256 · Cited by 64
Self-citation(2006) · Journal of Neurobiology · doi:10.1002/(issn)1097-4695 · Cited by 60
Decreased rabphilin 3A immunoreactivity in Alzheimer’s disease is associated with Aβ burden
Tan, M. G. K., Lee, C., Lee, J. H., Francis, P. T., Williams, R. J., Ramírez, M. J., Chen, C., Wong, P. T. ‐., & Lai, M. K. P. (2013) · Neurochemistry International · doi:10.1016/j.neuint.2013.10.013 · Cited by 50
Ramos‐Miguel, A., Jones, A. A., Sawada, K., Barr, A. M., Bayer, T. A., Falkai, P., Leurgans, S. E., Schneider, J. A., Bennett, D. A., & Honer, W. G. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.02.006 · Cited by 37
Self-citationRegulation ofcpg15 expression during single whisker experience in the barrel cortex of adult mice
Harwell, C. C., Burbach, B. J., Svoboda, K., & Nedivi, E. (2005) · Journal of Neurobiology · doi:10.1002/neu.20176 · Cited by 33
Proteomic analysis of mesenchymal to Schwann cell transdifferentiation
Sharma, A. D., Wiederin, J. L., Uz, M., Ciborowski, P. S., Mallapragada, S. K., Gendelman, H. E., & Sakaguchi, D. S. (2017) · Journal of Proteomics · doi:10.1016/j.jprot.2017.06.011 · Cited by 27
Postmortem MRI: a novel window into the neurobiology of late life cognitive decline
Dawe, R. J., Yu, L., Leurgans, S. E., Schneider, J. A., Buchman, A. S., Arfanakis, K., Bennett, D. A., & Boyle, P. A. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.05.023 · Cited by 26
Self-citationTeuling, E., Bourgonje, A. M., Veenje, S., Thijssen, K. L., de Boer, J., van der Velde, K. J., Swertz, M. A., & Nollen, E. A. A. (2011) · PLoS Currents · doi:10.1371/currents.rrn1255 · Cited by 24
Prats, C., Arias, B., Ortet, G., Ibáñez, M. I., Moya-Higueras, J., Pomarol‐Clotet, E., Fañanás, L., & Fatjó‐Vilas, M. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.11.017 · Cited by 23
Kim, N., Yu, L., Dawe, R. J., Petyuk, V., Gaiteri, C., Jager, P. L. D., Schneider, J. A., Arfanakis, K., & Bennett, D. A. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.07.013 · Cited by 20
Self-citationCao, M., Xu, W., Yu, J., Zheng, H., Tan, X., Li, L., Rui, Y., Xu, G., Cui, G., Xu, J., et al. (2013) · Journal of Molecular Histology · doi:10.1007/s10735-013-9517-4 · Cited by 15
Neuritin: A therapeutic candidate for promoting axonal regeneration
Shimada, T. (2013) · World Journal of Neurology · doi:10.5316/wjn.v3.i4.138 · Cited by 13
SGTb regulates a surface localization of a guidance receptor BOC to promote neurite outgrowth
Vuong, T. A., Lee, S.-J., Leem, Y.-E., Lee, J.-R., Bae, G., & Kang, J. (2019) · Cellular Signalling · doi:10.1016/j.cellsig.2019.01.003 · Cited by 10
Wingo, A. P., Fan, W., Duong, D. M., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/793349 · Cited by 4
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Johnson, E. C. B., Carter, E. K., Dammer, E. B., Duong, D. M., Gerasimov, E. S., Liu, Y., Liu, J., Betarbet, R., Ping, L., Yin, L., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-021-00999-y · Cited by 561
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Metadata
- Authors
- Yu, L., Tasaki, S., Schneider, J. A., Arfanakis, K., Duong, D. M., Wingo, A. P., Wingo, T. S., Kearns, N., Thatcher, G. R. J., Seyfried, N. T., Levey, A. I., De Jager, P. L., & Bennett, D. A.
- Affiliations
- Rush University Medical Center (US)
- Emory University (US)
- University of Illinois Chicago (US)
- Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, New York
- Corresponding author
- Yu, Lei
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2020-11-01
- Volume
- 77
- Issue
- 11
- Pages
- 1172
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC7330835
- OpenAlex
- W3039778201
- Cited by
- 127
- References
- 42
- Citations by year
- 2026: 13 · 2025: 27 · 2024: 28 · 2023: 19 · 2022: 24 · 2021: 13 · 2020: 2
- FWCI
- 10.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG017917, R01AG056533, R01AG015819, P30AG010161, P50AG025688)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- cognitive resilience, dorsolateral prefrontal cortex, proteome-wide association study, Alzheimer's disease, dementia, cognitive decline, community-dwelling older adults, NRN1, ACTN4, VGLUT1, SLC17A9
- MeSH terms
- Rabphilin-3A, Actinin, Adaptation, Psychological, Aged, Aged, 80 and over, Epoxide Hydrolases, Female, Humans, Male, Nerve Tissue Proteins, Neuropeptides, Proteins, Molecular Chaperones, Vesicular Transport Proteins, Adaptor Proteins, Vesicular Transport, Ubiquitin-Activating Enzymes, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Independent Living, GPI-Linked Proteins, Cognitive Dysfunction
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